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Description

This lecture reviews the key mechanisms behind anaphylaxis with a focus on second messenger pathways involved in the three main phases, critical mediators and the role of platelet activating factor.

Objectives

Learn the key second messenger pathways behind anaphylaxis

Allergen cross-linking of IgE bound to mast cells via high affinity receptors (FCeRI) leads to activation of tyrosine kinase (TK) second messenger pathways including: activation of PLC, producing diacylglycerol (DAG)/inositoltriphosphate (PI3) leading to the release of intracellular secretory granules and generation of cytokines; and activation of cPLA2 producing arachidonic acid and the precursor Lyso-PAF, that is eventually converted into PAF.

Learn the key role platelet activating factor plays in anaphylaxis

During anaphylaxis, PAF binding to its receptor (PAFr), leads to 2nd messenger pathways that initiate and amplify inflammation and thrombosis, increase vascular permeability contributing to massive fluid shifts and lead to marked vasodilation. One key PAF signaling pathway involving PIK3, increases eNOS activity and thus increases NO production leading to the marked vasodilation and hypotension associated with anaphylactic shock.

Know how manipulation of key mechanisms in anaphylaxis may provide novel therapies

PAFr antagonists significantly improve anaphylaxis outcomes in animal models. Absolute protection against fatal anaphylaxis (mice models) was noted by inhibiting PAF/PI3K and eNOS. Methylene blue, an inhibitor of soluble guanylate cyclase, that blocks NO mediated vasodilation, has been used as a novel therapy for the management of refractory anaphylaxis in humans. Treatment of anaphylaxis (mice models) with recombinant PAF-AH significantly reduced mortality (from 100% to 20%).

I am currently an Assistant Professor in Emergency Critical Care at Tufts University. I received my DVM degree from North Carolina State University:CVM and completed my ECC residency program at BluePearl Veterinary Partners in Tampa, FL where I obtained my DACVECC certification. I have a strong interest in exotic animal emergency critical care medicine and I am also interested in molecular and cellular mechanisms of critical illness with a focus on immune system dysfunction.

Current Accreditations

This course has been certified by or provided by the following Certified Organization/s: